Friday, May 12, 2017

The coronary calcium score ( for example as done with a EBCT heart scan) is well recognized as a tool to estimate cardiac risk, a higher score meaning a higher risk.

Coronary calcification is by definition coronary artery disease. Calcification may be in the media of arteries or in the intima. Intimal calcification may be dense as is found in fibrous, basically stable plagues which are not prone to rupture and cause an acute coronary event. Spotty calcification can be found in soft, vulnerable plaques that are at risk of rupture.

Serial calcium scans on patients taking statins have shown increase in coronary calcification and yet there is more than abundant evidence that statins ( at least in secondary prevention) can reduce plaques and decrease the risk of coronary events,a situation referred to by some as the "statin paradox" or the "plaque paradox".

A possible explanation to this alleged paradox may be found in a study (1) from Cleveland Clinic in which the authors analyzed intravascular ultrasound images of patients from 8 clinical trials.

Patients with coronary artery disease treated with statins show an increase in coronary calcification.The so-called high intensity statins bring about more increase in calcification while also causing the greatest regression of plaques. The increase in calcification may be one mechanism by which statin therapy stabilizes plagues and makes them less likely to rupture. So serial calcium scans in a patient taking a statin demonstrating increased calcification may not be a warning of increased risk at all.

Quoting Cleveland Clinic's Dr . Steve Nissen:

"This is an important observation that tells us statins work to stabilize plaques by converting softer,cholesterol -laden plaques that are prone to rupture into more stable calcified plaques that are relatively inert.It explains the paradox of why serial measurements of calcium doesn't necessarily work to track the progression of disease and it explains to some extent how statins work.

Internists who like to talk about mechanisms and how things work may find this a compelling story but as an accompanying editorial (3) said this is a hypothesis generating study,causality cannot be inferred and the techniques used have multiple limitations. Human are pattern seeking story telling creatures and this story might catch on-at least until something better comes along.

Shifting gears-there are at least 3 articles that have reported that long time endurance exercisers have higher calcium scores than age matched sedentary controls controls,an observation offered by some authors as more proof that too much exercise is not good. Juxtaposed to that is the epidemiologic evidence that longtime endurance exercise decreases the risk of a coronary event and that elite athletes life longer than sedentary colleagues and yet more calcium in the athletes.Another plaque paradox?

Merghani and co-authors studied 152 maters athletes ( ages 51-63) They found that "most" )( 60%) of the lifelong exercisers has a normal CT coronary angiogram as did a similar number of the controls. However they also reported that the male athletes were more likely to have a CAC score of 300 or more compared to the sedentary controls.The plaques in the athletes were predominately calcific.

Similar results were reported by V.L. Aengevaeren et al (2) who studied 284 lifelong exercisers. In regard to their findings they said:

"The most active group did however had a more benign composition of plaques with fewer mixed plaques and more often only calcified plaques.These observation may explain the increased longevity of endurance athletes despite the presence of more coronary atherosclerotic plaques in the most active participants ".

Eijsvogels and co-workers published an excellent, detailed and extensively referenced review( 4) of the possible harmful effects of acute and chronic exercise . They only briefly mention what was then the preliminary evidence that longtime runners have higher calcium scores as their review preceded Puri's work as well as that of Aengevaren and Merghani

Tuesday, May 09, 2017

The longitudinal decline in aerobic capacity is typically said to be 5 -10% per decade from age 40 to about age 70 then a more rapid decline occurs. Data from the Baltimore Longitudinal study of Aging (BLSA) (1) suggests that the decline is not constant across age ranges but rather" accelerates markedly with each successive age decade".

How so?

In cross sectional studies " each succeeding age decade represents a more highly selected group than it predecessor, thus healthy 70 to 90 year-olds may have been physiologically superior to current 20-40 years olds when they were on a similar age. In other words there is inherent selection bias in cross sectional data.

I will not attempt to explain the statistical model used but here are their values for the reduction in men in peak O2 uptake expressed in ml/kilo/min for various decades:

They found that the oxygen pulse (oxygen consumed per heart beat) rate of decline mirrored the rate of decline in peak 02 .Since oxygen pulse is a function of stroke volume and peripheral muscle uptake of oxygen it is not possible to determine if it is cardiac output or muscle uptake that is largely responsible for the decline.

Caveat-The published results are from a mixed-effect prediction model and the median followup was only 7.9 years and prediction is the operative word. Though the study is "longitudinal",numbers in their tables do not represent for example following the same people over a lifetime and noting the per decade change in oxygen uptake. Still their data suggest that the often quoted 5-10 % decrease per decade may be too optimistic and rates of changes likely accelerate with aging.The confidence intervals for each age range are quite large and you have to wonder what are the mechanisms responsible for such wide variation in loss of exercise capacity within an age range. If subendocardial fibrosis is the ( or a) culprit what are the factors that accelerate or retard that process.